Lauryl pyridinium salt of 5-chloro-2-mercaptobenzothiazole and tri- and dibrominatedsalicylanilides bactericide composition



3,240 710 LAYL PYRIDINIUM SALT F S-CHLORU-Z- MERCAPTOBENZOTHTAZULE AND TRI- AND DlBRUMHNATED SALICYLANELHDES BACTERE- CHDE COMPQSETION Lee R. Schiltz, Harvey, lil., assignor to Swift dz (Zornpany, Chicago, Ill., a corporation or Hllinois No Drawing. Filed June 15, 1962, Ser. No. 202,706 1 Claim. (Cl. 252-106) The present invention relates, in general, to a method for providing substantially bacteria-free materials which possess residual antibacterial properties. More particularly, the invention is directed to a washing compound containing a mixture of ingredients with substantivity for fabric, which compound will render materials washed therewith substantially self-sanitizing or capable of killing bacterial growth subsequently encountered due to the presence of active residual amounts of said mixture of ingredients.

There is an increasing consciousness among the population of the dangers of bacterial contamination and the variety of ways in which the individual can be exposed to bacteria. F or example, hospital-acquired Staphylococcus infections are no longer looked upon as an isolated problem of the practicing physician or hospital administrator. Rather, the emergence of antibiotic resistant strains of staphylococci and of specific epidemic strains has posed a concurrent threat to hosiptal populations and the community at large, such that the prevention and control of staphylococcal disease is currently looked upon as a community health problem. With this public awareness, there is an increasing demand for substances which can be effectively used to treat surfaces suspected of past or future exposure to bacteria in order to control the bacterial population.

Articles subjected to good laundering procedures will be substantially bacteria-free and if protected from contamination prior to use, will remain so until used. However, if not protected prior to use, the article may, and probably will, become contaminated with bacteria at that time, either through air-borne bacteria or contact with personnel handling the articles, and in any event when used will lose its sterility.

One particularly susceptible area for bacterial contamination is clothing, bedding, dishes, glassware, kitchen utensils, etc. Hospitals, hotels, institutions, laundries and the like which deal with large quantities of such washable articles that may be or may become bacterially contaminated could make good use of a compound that could easily be employed in the cleaning of those articles to render them substantially bacteria-free and, also self-sanitizing in regard to subsequent recontamination with bacteria.

It is, therefore, an object of this invention to provide a method for producing substantially bacteria-free materials that will be resistant to growth of bacteria subsequently encountered, i.e., self-sanitizing.

An additional object of the invention is the provision of an unusually effective bactericidal mixture of ingreclients.

A further object is to provide an easy method for bringing articles susceptible to bacterial contamination into contact with an antibacterial mixture to render them substantially self-sanitizing.

nited States Patent 0 M 3,240, Patented Mar. 15, 1966 A still further object is to provide a method for providing dormant antibacterial properties in washing goods, which properties will manifest themselves upon subsequent bacterial contamination of the goods.

An additional object is to provide a washing compound that will incorporate dormant antibacterial properties in articles washed therewith.

Additional objects and advantages will become apparent to those skilled in the art from a reading of the following description of the invention.

In general, this invention relates to the discovery that by washing articles in the manner and with the composition subsequently described it is possible to incorporate into the article a residual amount of antibacterial agent suflicient to inhibit the growth of bacteria when the article is subjected to conditions which would normally favor the growth of bacteria. When treated in the manner proposed, the article retains its self-sanitizing properties even after use and actual contact with the virulent bacteria.

More specifically, the invention comprises a composition comprising a small amount of lauryl pyridinium 2-(5- chlorobenzothiazyl)-sulfide and a mixture of polyhalosalicylanilides to reduce growth of certain species of bacteria and, more particularly, to produce a 99.5% reduction of Staphylococcus count in soiled articles. In this regard, it is pointed out that in soap use for laundering, the lauryl-pyridinum salt of 5-chloro-2-mercaptobenzothiazole will allow staphylococcal growth on cloth massively inoculated therewith. Nevertheless, and contrary to the expected result, it has been discovered that a small residual amount on washed cloth of the mixture of the above active ingredients results in a remarkable percentage kill of staphylococci.

In general, lauryl pyridinium 2-(5-chlorobenzothiazyl)- sulfide can be produced by reacting 5-chloro-2-mercaptobenzothiazole with a lauryl pyridinium salt usually in an aqueous medium. For example, a solution of lauryl pyridinium chloride dissolved in water can be added to an equal molecular amount of the sodium salt of 5- chloro-2-mercaptobenzothiazole which is formed by the neutralization of the thiazole with sodium hydroxide. The precipitate which is formed is then filtered and the final product is a yellow, waxy, solid product. Also, 5- chloro-2-1nercaptobenzothiazole can be reacted with lauryl pyridinum hydroxide.

The halosalicyl anilides can be prepared by reacting halogenated anilines with the corresponding salicylic compound. The halogenated isomers may vary in proportions; however, it has been found that the trihaloisomers should be present in amounts of about 95% of the total mixture of halogenated isomers. A mixture of halogenated isomers of salicylanilide composed of about 80- of 3,5,4-tribromosalicylanilide and about 205% of 3,5 dibromosalicylanilide and/or 5,4'-dibromosalicylanilide is typical. Normally, in a 95:5 grade the 5,4-isomer is present in an amount of about 12% and the 3,5-isomer in the amount of 3%. In a 80:20 grade, a typical composition comprises about 80% 3,5,4'tribromosalicylanilide, and 20% 3,S-dibromosalicylanilide with less than 1% of the 5,4'-dibromosalicylanil-ide. Similar results are obtained, however, with other diand trihalosalicylanilides such as triiodo, trichlorosalicylanilide and the like.

While materials laundered with our improved washing compound are no more resistant to contamination during storage than other fabrics, the active anti-staphylococcal agents are stable during dry storage of fabrics and subsequent moistening of the fabrics washed in the compound brings the dormant anti-staphylococcal activity into play. Thus, as would be expected in a hospital environment when towels, wash cloths, bed linens, and clothing are used by a patient, the fabric becomes contaminated both by contact with the skin of the patient and the environment itself. When such contamination is accompanied by moisture in the form of perspiration, urine, pus, blood, water or the like, there may be sufficient organic material on the fabric to support the growth of the contaminating bacteria. The active residual concentrations of the mixture of antibacterial agents incorporated in fabrics washed in laundering compounds of the instant invention not only prevent this multiplication but in fact have a dramatic ability to destroy staphylococci on contact. The substantivity of the mixture of antibacterial agents for fabric and the lack of solubility in water is of considerable importance. These characteristics allow the active agents to be fixed to the fabric and they do not leach out during normal use of such things as towels and Wash cloths.

The soap product into which the antibacterial mixture is incorporated is somewhat a matter of choice. However, it has been found that an especially effective cleaning compound imparting unusually effective antibacterial properties can be produced by mixing the antibacterial ingredients in a built soap. An example of such a soap is one that contains approximately equal major amounts of soap solids and sodium metasilicate, together with minor amounts of soda ash, tetrasodium pyrophosphate, moisture and volatile matter and trace amounts of an oil and any of the common optical bleaching agents.

Other suitable washing compounds into which the unusual eifective antibacterial compound can be incorporated are dry and liquid detergents and built detergents. An example of an approximate formulation for a dry, built detergent would be the following:

28% active alkyl aryl sulfonate 25% tetrasodium pyrophosphate 25 sodium tripolyphosphate 21% sodium sulfate 1% carboxymethyl cellulose Trace amounts of perfume and an optical bleach A representative liquid, built detergent into which the mixture is effectively incorporated includes:

21% potassium pyrophosphate 27 potassium lauryl sulphate 5.5% potassium silicate 5% sodium toluene sulfonate 1% carboxymethyl cellulose Trace amounts of optical bleach with the remainder being water The antibacterial mixture can also be added to 100% active compounds such as amine condensates and the like.

Extremely small amounts of the residual antibacterial mixture are effective, on the order of about 1 p.p.m. to 5 p.p.m. based on the washing compound. When incorporated into a soap product, it has been found that a mixture of from .05% to .5% of lauryl pyridinium 2-(5-chlorobenzothiazyD-sulfide plus .05 to .5 of the halogenated salicylanilides based on the weight of the soap to be an optimum for depositing the required residual amount in the washed articles. Lesser amounts can be used with diminishing efficiency. Amounts up to about 1% of each active ingredient have been found very effective. Greater amounts than this are not increasingly more effective to Warrant the added expense. Specifically, it has been found that a mixture of .25% of the thiazole plus .25% of the halogenated salicylanilides based on the weight of the soap is an optimum for depositing the required residual amount. Other active ingredients such as 2,2-dihydroxy 3,5,6-3,5,6-hexachlorodiphenyl methane may also be added, if desired. For example, superior results have been found when the active ingredient mixture comprises .25% of the thiazole, .25 of the halogenated salicylanilides, and .05 of the dihydroxy hexachlorodiphenyl methane.

The length of time that an article is subjected to the antibacterial-containing mixture is unimportant so long as there is actual contact of the article with the antibacterial agent. While applicant does not want to be limited to any particular theory as to how the antibacterial agent acts, it appears that at least insofar as cloth is concerned it is at least partially substantive to the cloth and it actually becomes imbedded in the cloth fibers since it exhibits a residual antibacterial effect after the cloth has been washed. A l p.p.m. residual amount of the antibacterial mixture is sufficient to render cloth substantially free of many viable bacteria and self-sanitizing.

The following data is presented to illustrate the invention only and should not be construed as imposing limitations on the scope of the invention apart from those delineated in the appended claim.

For the purpose of measuring the residual antibacterial effectiveness of articles washed with a washing compound containing the antibiotic mixture, the contact plate method was used. This procedure involves inoculation of the surface of a sterile agar medium with a mixture of staphylococci.

EXAMPLE I A 2024 hour broth culture of a coagulase positive Staphylococcus aureus was used to inoculate poured plates of tellurite glycine agar medium. About 20 milliliters of the medium was poured into Petri dishes and allowed to harden before adding 0.1 milliliter of the Staphylococcus culture. 5 staphylococci strains which were grown separately, but mixed prior to inoculating the plates, were utilized. The culture was spread over the surface of the medium using previously sterilized hockey sticks. The plates were held for about 24 hours after pouring the medium so as to allow the surface to dry and facilitate the spreading of the culture. One square inch of the cloth to be tested was then placed on the inoculated medium and by means of a hockey stick was pressed so as to produce close contact with the medium. A duplicate plate using untreated cloth as a control was used at the same time. The plates were incubated at 37 C. for about 24 hours. Properly washed cloth inhibited bacterial growth under the square inch piece of cloth, but did not necessarily show a zone around the edges where the staphylococci have failed to grow. The control plate with the untreated cloth showed growth over the entire surface of the plate. The absence of a zone of inhibition around the cloth washed with a soap containing the active ingredients of this invention is a clear reflection of the substantivity of the anti-bacterial agent for fabric and their resistance to leaching.

In order to evaluate the effect of the different active agents for bacterial inhibition properties, a factorial experiment was used. The fully balanced factorial experiment was carried out using an isomeric mixture of halogenated salicyl anilides wherein the 3,5,4'-tribromosalicylanilide was present in the amount of The experiment was replicated in its entirely using the same level, but using an isomeric mixture of halogenated salicyl anilides wherein the tribromo isomer totaled about The following table is typical of the results obtained when the instant bactericides were added to the base soap and tests conducted to determine the substantivity thereof:

5 T able I Amount, percent Percent Inhibition V-426 TBS 1 2nd 3rd 4th and 2 Wash Wash Wash 0.5 25 50 75 0. 5 Slight 25 50 0. 5 100+ 100 100- V-426=lauryl pyridiuum salt of 5-ch10ro-2-mercaptobenzothiazole.

TBS 1=80% 3,5,4-trlbromosa1icylanilide and 20% 3,5-dibromo and 5,4-dibromo isomers.

TBS 2=95% 3,5,4-tribromo and 5% 3,5- and 5,4-dibromosalicylanilide.

The test procedure as set up was a threshold test. It was developed in the laboratories so that minor diiferences in results could be detected. They should not be interpreted as the exact type of result that would be obtained in a commercial laundry wash wheel or laundry equipment. However, the results obtained clearly show that the substantivity is intimately associated with a synergistic property of the two active ingredients.

The use of the active ingredients of the instant invention will result in a clean fabric having the inherent ability to sanitize itself. By the use of the phrase substantially free of bacteria I do not intend to convey the meaning that no bacteria will ever be present. What is meant is that the vast majority of bacteria will be removed from the materials during the washing operation. Certain heat-resistant spores may survive and remain on the washed goods. Nevertheless, for all practical purposes the material out of the washer will be substantially free of bacteria. However, when the material that has been washed with a soap containing the antibacterial mixture is further contaminated (as, for example, from the en vironmental air, contact with contaminated storage facilities, contact with a hospital patient, etc.), and is sub sequently moistened in some manner, the residual antibacterial activity imparted to the cloth will inhibit the growth of any bacteria present.

Obviously, many modifications and variations of the invention as hereinbefore set forth may be made without departing from the spirit and scope thereof, and therefore only such limitations should be imposed as are indicated in the appended claim.

I claim:

A cleaning composition for fabric adapted to incorporate unusually effective residual antistaphylococci and self-sanitizing properties in fabric cleaned therewith, which comprises: a cleaning composition having incorporated therein about .25 based on the weight of the composition, of the lauryl pyridinium salt of 5-chloro-2- mercaptobenzothiazole and about .25 based on the weight of the composition, of a mixture of brominated isomers of salicylanilide composed of about of 3,5,4-'tribromosalicylanilide and about 5% of a mixture of 3,S-dibromosalicylanilide and 5,4-dibromosalicylanilide.

References Cited by the Examiner UNITED STATES PATENTS 1,962,109 6/1934 Alvord 16733 2,555,024 5/1951 Brooks 167-33 2,879,200 3/1959 Kosmin 167-33 2,906,711 9/1959 Stecker 167-31 3,057,920 10/ 1962: Schrarnm 167'31 JULIAN S. LEVITT, Primary Examiner. 

